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Projekt
Cross-Pathway Control, Nitrogen Metabolism and their Role in Pathogenicity of Aspergillus fumigatus
Antragsteller
Professor Dr. Sven Krappmann
Fachliche Zuordnung
Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
Förderung
Förderung von 2004 bis 2011
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5426824
Aspergillus fumigatus is the primary mold pathogen causing Aspergillosis, especially in immunocompromised individuals. We have shown that the metabolic transcriptional regulator protein CPCA is required for its full virulence. In other fungi, this transcription factor represents a master regulator affecting gene expression of a network of hundreds of genes, termed the Cross-Pathway Control response. Mutant A. fumigatus strains deleted in the corresponding cpcA genetic locus display significantly reduced mortality rates in a murine model of pulmonary aspergillosis. The goals of this proposal are: (1) We will analyse whether varying amounts of CPCA have an influence on virulence capacities. Therefore we will introduce various mutant alleles of the cpcC-encoded sensor kinase, which controls the degree of CPCA expression. (2) We will identify direct target genes of the transcriptional activator CPCA in A. fumigatus by chromatin immunoprecipitation (ChIP) and analyse which of them are required for full virulence of this opportunistic pathogenic fungus. This analysis of CPCA downstream components will be accompanied by proteome analyses.
DFG-Verfahren
Schwerpunktprogramme
